Characterization and secondary structure analysis of endostatin covalently modified by polyethylene glycol and low molecular weight heparin.

J Biochem

Institute of Biochemical and Biotechnological Drug, School of Pharmaceutical Science, National Glycoengineering Research Center, Shandong University, and Jinan Central Hospital and Clinical Medical College of Shandong University, Jinan, China.

Published: August 2008

Endostatin (ES), as an angiogenesis inhibitor, has been approved by the State Food and Drug Administration (SFDA) in China for the treatment of patients with non-small-cell lung cancer. However, as a protein drug, there are a lot of obstacles on its clinical application, such as need of high dose to maintain its efficacy, expensive and poor stability, etc and limits its clinical use. In order to overcome these shortcomings, we chemically modified ES by polyethylene glycol and low molecular weight heparin (LMWH), respectively. The changes of the secondary structure of the modified products were studied by Fourier transform infrared spectroscopy and Circular dichroism spectra to obtain better ES derivatives. Our study demonstrated that the modified products have a better heat tolerance than ES towards. The result of secondary structure analysis suggests the percentage of beta-turn in whole protein is an important factor on the activity and heat stability and ES modified by LMWH can maintain higher activity and its secondary structure.

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http://dx.doi.org/10.1093/jb/mvn060DOI Listing

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